Breadcrumb

This Manual has been designed for use in the NICU at London Health Sciences Centre (LHSC), London, Ontario, Canada, and represents clinical practice at this institution. The information contained within the Manual may not be applicable to other centres. If users of this Manual are not familiar with a drug, it is recommended that the official monograph be consulted before it is prescribed and administered. Any user of this information is advised that the contributors, Editor and LHSC are not responsible for any errors or omissions, and / or any consequences arising from the use of the information in this Manual.

Clonidine

Indication

Adjunct medication used in the management of neonatal abstinence syndrome that results from opioid exposure

Pharmacology

Chronic opioid exposure suppresses catecholamine release in various parts of the brain. Abrupt discontinuation of the opioid results in a rebound increase in the release of catecholamines. This surge of catecholamine release is responsible for the onset of withdrawal symptoms (NAS)

At low doses, clonidine preferentially stimulates a2-adrenergic receptors, located presynaptically in the midbrain and medulla. The resulting effect is a decrease in the release of catecholamines and an attenuation of many of the symtoms of NAS.

Well absorbed after oral administration

Highly lipid soluble

40-60% is eliminated unchanged by kidneys

Adverse Effects

Hypotension

Bradycardia / tachcardia

Rebound hypertension if abruptly discontinued

Sodium and water retention

Constipation

Precautions

Some studies gradually increased doses over 1 to 2 days to begin therapy, and tapered doses by 0.25 mcg/kg every 6 hours to discontinue (or by 25% of the total daily dose every other day).

However, clonidine has also been started and stopped abruptly with no adverse effects.

Adjust doses in patients with renal insufficiency

Special Note

Three deaths in the clonidine group were reported by the only prospective RCT on Clonidine vs Placebo (Agthe 2009). The deaths occurred after hospital discharge but before 2 months of age. Excluding the death from methadone overdose (homicide), the other two deaths were believed to be due to myocarditis and SIDS, respectively. All deaths were reported to the Food and Drug Administration and the Data Safety and Monitoring Board, which deemed the deaths not likely attributed to clonidine exposure, and the study was allowed to continue.

Dose

NEONATAL ABSTINENCE SYNDROME THERAPY

0.5 - 1 mcg/kg, given orally every 4-6 hours

Much higher doses (0.5 to 3 mcg/kg/h) have been used as a continuous infusion (Reference # 6)

Adequate clinical trials to establish an efficacious and safe dose still are required